Many present systems for delivering active agents to targets are severely limited by biological, chemical, and physical barriers, which are imposed by the environment through which delivery occurs, the environment of the target itself, or the target itself. Delivery is also limited, in many instances, by the chemical nature of the active agent. For example, oral delivery is generally ineffective with active agents that are poorly water-soluble.
The imidazole derivative family of compounds is particularly effective against a broad range of fungal infections such as those caused by Trichophyton rubrum, Tricophyton mentagrophytes, Epidermophyton floccsum, and Candida albicans, but these compounds are either partially water soluble or insoluble in water. For example, the solubility of itraconazole in water is less than 0.00001 g/ml.
Partially because imidazole derivatives are typically insoluble in water, they are difficult to administer orally. Consequently although imidazole derivatives are frequently prescribed for the treatment of fungal infections, they have been available only in topical preparations or in oral formulations with limited bioavailability.
In recent years, fungal infections, such as those caused by Candida albicans in particular have become more prevalent and intractable due to their appearance in immunocompromised patients, such as those infected with Human Immunodeficiency Virus (HIV) or those suffering from Acquired Immunodeficiency Syndrome (AIDS).
For example, U.S. Pat. No. 3,717,655 discloses imidazole derivatives which have antifungal and antibacterial activity. These compounds are almost insoluble in aqueous solutions such as water and are very poorly soluble in polar solvents such as ethanol.
Das et al., U.S. Pat. No. 4,912,124, disclose a solvent system for imidazole derivatives that include mixtures of a polar solvent, a polyhydric alcohol that acts as a solubilizing agent, a nonionic or amphoteric surfactant, and a cosmetic humectant. Solutions containing at least 1 percent by weight of the imidazole derivatives can be formulated using this solvent system. However, these formulations are suitable for external topical use only.
Accordingly, there is a need for orally deliverable forms of imidazole derivative antifungal agents.